alpha-amanitin resistance in Drosophila melanogaster: A genome-wide association approach

作者：Mitchell Chelsea L; Latuszek Catrina E; Vogel Kara R; Greenlund Ian M; Hobmeier Rebecca E; Ingram Olivia K; Dufek Shannon R; Pecore Jared L; Nip Felicia R; Johnson Zachary J; Ji Xiaohui; Wei Hairong; Gailing Oliver; Werner Thomas^*

来源：PLos One, 2017, 12(2): e0173162.

DOI：10.1371/journal.pone.0173162

We investigated the mechanisms of mushroom toxin resistance in the Drosophila Genetic Reference Panel (DGRP) fly lines, using genome-wide association studies (GWAS). While Drosophila melanogaster avoids mushrooms in nature, some lines are surprisingly resistant to alpha-amanitin-a toxin found solely in mushrooms. This resistance may represent a pre-adaptation, which might enable this species to invade the mushroom niche in the future. Although our previous microarray study had strongly suggested that pesticide-metabolizing detoxification genes confer alpha-amanitin resistance in a Taiwanese D. melanogaster line Ama-KTT, none of the traditional detoxification genes were among the top candidate genes resulting from the GWAS in the current study. Instead, we identified Megalin, Tequila, and widerborst as candidate genes underlying the alpha-amanitin resistance phenotype in the North American DGRP lines, all three of which are connected to the Target of Rapamycin (TOR) pathway. Both widerborst and Tequila are upstream regulators of TOR, and TOR is a key regulator of autophagy and Megalin-mediated endocytosis. We suggest that endocytosis and autophagy of alpha-amanitin, followed by lysosomal degradation of the toxin, is one of the mechanisms that confer alpha-amanitin resistance in the DGRP lines.

• 出版日期2017-2-27